Given the emerging demand to“escape from flatland”for modern medicinal chemistry,both the catalytic construction of complex three-dimensional molecular architectures from planar aromatics and the bioisosteric substi...Given the emerging demand to“escape from flatland”for modern medicinal chemistry,both the catalytic construction of complex three-dimensional molecular architectures from planar aromatics and the bioisosteric substitution of aromatic ring with bicyclo[2.1.1]hexanes(BCHs)become increasingly valuable.Despite notable advancements in the cycloaddition reactions involving bicyclo[1.1.0]butanes(BCBs)and2 π-components,the application of easily accessible aromatic compounds in these transformations,particularly in an asymmetric manner,is still relatively unexplored.Herein,we report a nickel-catalyzed enantioselective polar dearomative(3+2)cycloaddition of BCBs with benzazoles and indoles.This protocol offers an efficient route for the synthesis of N,S-or N,N-heterocycles decorated fused aza-BCHs bearing two quaternary carbon centers.This approach stands out for its practicality and appeal due to the utilization of easily accessible starting materials and catalysts,broad substrate scope,easy scalability,and the employment of mild reaction conditions.Density functional theory(DFT)calculations offer crucial insights into the reaction mechanism and elucidate the factors governing the enantioselectivity within the dearomative cycloaddition process.展开更多
基金the National Natural Science Foundation of China(No.22471068 to J.-J.Feng,No.22273035 to G.Q.Wang)Fundamental Research Funds for the Central Universities for financial support+1 种基金the High-Performance Computing Center(HPCC)of Nanjing Universitythe financial support by Engineering Research Center of Photoresist Materials,Ministry of Education。
文摘Given the emerging demand to“escape from flatland”for modern medicinal chemistry,both the catalytic construction of complex three-dimensional molecular architectures from planar aromatics and the bioisosteric substitution of aromatic ring with bicyclo[2.1.1]hexanes(BCHs)become increasingly valuable.Despite notable advancements in the cycloaddition reactions involving bicyclo[1.1.0]butanes(BCBs)and2 π-components,the application of easily accessible aromatic compounds in these transformations,particularly in an asymmetric manner,is still relatively unexplored.Herein,we report a nickel-catalyzed enantioselective polar dearomative(3+2)cycloaddition of BCBs with benzazoles and indoles.This protocol offers an efficient route for the synthesis of N,S-or N,N-heterocycles decorated fused aza-BCHs bearing two quaternary carbon centers.This approach stands out for its practicality and appeal due to the utilization of easily accessible starting materials and catalysts,broad substrate scope,easy scalability,and the employment of mild reaction conditions.Density functional theory(DFT)calculations offer crucial insights into the reaction mechanism and elucidate the factors governing the enantioselectivity within the dearomative cycloaddition process.
